**5. Beneficial microbes in the gut; effects on antibiotic resistant strains**

In the gut lies a community of beneficial microorganisms that have carved a niche and have evolved with humans over several generations—collectively known as the gut microbiota. Microorganisms that make up the gut microbiota include members of bacteria, fungi, viruses, archaea, and protists. Before the advent of next-generation sequencing technologies, very little was known about the composition and functions of this microbial community, and as such were not thought as agents to be considered in health and disease. Now, we are just beginning to scratch the surface of the potentials of this novel 'organ', and its implication in the overall health of humans. It is referred to as an 'organ' because the gut microbiome (the gut microbiota, gut microbial genomes, and the living environment) is made of millions of bacterial cells that collectively weigh about 1.5 kg, possesses about 150 times more genes than human genes, and contribute significantly to human health. As a result of advances in research, scientists are beginning to appreciate the beneficial roles of gut microbes, and their symbiotic relationship with us, their host. Although previously thought to be responsible for the production of essential vitamins B and K alone, the gut microbiota has been discovered to be implicated in various aspect of human health, and its effects extend beyond the gastrointestinal tract through the release of biosynthesized metabolites (by the gut microbes) from the gut into the systemic circulation. For example, the response of immune cells to inflammation is modulated by the gut microbiota [55]. The effect of these metabolites extends even to the central nervous system where they influence behavior, mood, and emotions.

because an imbalance in the structure of the gut microbiota is a risky phenomenon in the development of gastrointestinal and extra-gastrointestinal diseases. Antibiotics do not differentiate between beneficial bacteria and pathogenic bacteria, and as such, there is a significant decrease in the richness and diversity of the gut microbiota after antibiotic administration. This places a fatal dent on gut microbiota stability and creates an environment for opportunistic pathogens such as antibiotic-associated *Clostridium difficile* to thrive resulting in diarrhea. Dysbiosis (impairment in the natural balance) of the gut microbiota has been associated not only with the risk of antibiotic-associated diarrhea, but a plethora of other diseases such as type 2 diabetes, cancer, obesity, inflammatory bowel diseases and irritable bowel syndrome [59]. Adulthood is generally characterized by a stable gut microbiota, with occasional shifts in gut microbial diversity due to change in dietary habits, medication, illness or travel. On the other hand, the gut microbiota of infants is quite volatile and changes rapidly depending on the mode of birth, whether they are breast-fed or formula-fed, and whether they have been weaned or not. By the age of 2–5 years, their gut microbiota begins to resemble that of a typical adult. At the tail end of life, age-related changes in physiology of the body and changes in dietary habits due to loss of dentition could have a negative impact on the gut microbiota thereby making it less stable [60]. At this age also, the use of medication is high because they are more prone to diseases and impairments, which could influence gut microbial profiles. All of these factors mentioned above have to be considered when designing strategies aimed at

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The beneficial role played by bacteria in ingested fermented foods was linked to increased longevity in Balkans [61]. The administration of probiotics has also reduced the shedding of a pathogenic serotype of *E. coli* (*E. coli* O157: H7) by farm animals, thereby reducing the spread of these resistant strains from animals to humans who handle them regularly [62]. Also, there is hope that probiotics wills soon replace antibiotics in the veterinary field to treat diseases of farm animals while enhancing the growth of these farm animals. This way, antibiotic-resistant zoonotic pathogens do not re-emerge and enter the food chain. Also, the cost of production and maintenance of livestock will drop significantly if probiotics are being utilized rather

Researchers and clinicians are getting conscious of the fact that probiotics isolated from the host have a higher tendency to remain endogenous when administered than probiotics gotten from other sources. This fact informs their decision on the choice of probiotics to be administered. Capsules of probiotics are sometimes used in concert with antibiotics to treat particular diseases with greater effect than if either of them (probiotics or antibiotics) was used alone [17]. This co-administration is done with the hope that this action will reduce antibiotic selective pressure, and decrease the emergence of drug-resistant pathogens. Currently, research is ongoing on the packaging of lyophilized lactic acid bacteria into capsules so that they can be used in the veterinary field (as probiotics) to inhibit the proliferation of zoonotic pathogens [36]. This method will limit the spread of diseases from animals to humans through

restoring or contributing to the natural balance of the gut microbiota.

**6. Current applications**

than antibiotics.

In the gastrointestinal tract, the gut microbiota protects the gut against invading pathogens by competing with them for nutrients and attachment site. Most of the antibiotic-resistant disease-causing infectious agents that invade the gastrointestinal tract are food-borne or water-borne, and they include *Salmonella*, *Shigella*, *Campylobacter*, and *Listeria monocytogenes*. On the other hand, the gut microbiota is dominated by members of the Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Other less dominant bacterial phyla include the Fusobacteria, Tenericutes, Spirochaetes (differentially abundant in the gut of hunter-gatherers and rural individuals who consume plant-based foods), Elusimicrobia, and Verrucomicrobia. *Prevotella*—a member of the phylum Bacteroidetes—has also been found to be more abundant in individuals whose lifestyle resembles those of the Paleolithic (such as the hunter-gatherers) and Neolithic (such as the subsistence agriculturalists) era. Conversely, *Bacteroides*—another member of Bacteroidetes—is more abundant in populations that practice a westernized lifestyle, characterized by high-fat, low-fiber diet. Many of the gut commensals such as *Eubacterium*, *Ruminococcus*, *Roseburia*, and *Faecalibacterium* are members of the Firmicutes that produce short-chain fatty acids (such as butyrate, acetate, and propionate) as a product of microbial fermentation (the breakdown of complex polysaccharides), and these acids diminish diarrhea and gastrointestinal inflammation. These short chain fatty acids (SCFA) also create a harsh environment for the colonization of invading gastrointestinal pathogens by the reduction of intestinal pH. Other pathogen-inhibiting metabolites produced by gut commensals include phenols, ammonia, bacteriocins, and ammonia [56].

The composition of the gut microbiota can be positively or negatively affected by dietary habits and other lifestyle factors, the use of antibiotics, age, the state of health, and surgery amongst other factors [57]. The regular consumption of a fiber-rich, plant-based diet improves the compositional profile of the gut microbiota in terms of richness and diversity, and also improves the functional capabilities of the members of the gut microbiota. Good lifestyle practices such as the consumption of fiber-rich foods and fruits increases the relative abundance of beneficial gut microbes which produce metabolites that are responsible for overall gut epithelial health [58]. The impact of diet on the stability of the gut microbiota cannot be overemphasized. This is because an imbalance in the structure of the gut microbiota is a risky phenomenon in the development of gastrointestinal and extra-gastrointestinal diseases. Antibiotics do not differentiate between beneficial bacteria and pathogenic bacteria, and as such, there is a significant decrease in the richness and diversity of the gut microbiota after antibiotic administration. This places a fatal dent on gut microbiota stability and creates an environment for opportunistic pathogens such as antibiotic-associated *Clostridium difficile* to thrive resulting in diarrhea. Dysbiosis (impairment in the natural balance) of the gut microbiota has been associated not only with the risk of antibiotic-associated diarrhea, but a plethora of other diseases such as type 2 diabetes, cancer, obesity, inflammatory bowel diseases and irritable bowel syndrome [59]. Adulthood is generally characterized by a stable gut microbiota, with occasional shifts in gut microbial diversity due to change in dietary habits, medication, illness or travel. On the other hand, the gut microbiota of infants is quite volatile and changes rapidly depending on the mode of birth, whether they are breast-fed or formula-fed, and whether they have been weaned or not. By the age of 2–5 years, their gut microbiota begins to resemble that of a typical adult. At the tail end of life, age-related changes in physiology of the body and changes in dietary habits due to loss of dentition could have a negative impact on the gut microbiota thereby making it less stable [60]. At this age also, the use of medication is high because they are more prone to diseases and impairments, which could influence gut microbial profiles. All of these factors mentioned above have to be considered when designing strategies aimed at restoring or contributing to the natural balance of the gut microbiota.
